Κυριακή 1 Σεπτεμβρίου 2019

Recent Advances in Pharmacological Treatments of Adult Dermatomyositis

Abstract

Purpose of the Review

Dermatomyositis (DM) is an uncommon autoimmune disease that primarily affects the skin, muscle, and/or lungs, and remains a therapeutic challenge. We discuss recent studies evaluating efficacy of conventional treatments for clinically amyopathic DM (CADM), DM-associated interstitial lung (ILD) disease, and classic DM (CDM). We highlight several emerging new therapies with a focus on clinical trials, systematic reviews, and case series in the last 5 years.

Recent Findings

Recent studies report a significant number of patients remain refractory to antimalarials and require second- and third-line agents. Effective treatment for DM-associated ILD can vary based on patient specific antibodies. CDM requires oral glucocorticoids; recent studies have evaluated the benefits of adjunctive therapies including methotrexate and calcineurin inhibitors. New therapies target cell populations or cytokines thought to drive disease pathogenesis.

Summary

Dermatomyositis is an autoimmune disease that remains challenging to treat. Many patients are refractory to conventional therapies, warranting the development and evaluation of new treatments.

Synovial Tissue: Cellular and Molecular Phenotyping

Abstract

Purpose of Review

This review provides a summary of recent molecular findings that have refined our understanding of the cell types that constitute human synovial tissue, particularly in patients with rheumatoid arthritis (RA).

Recent Findings

Recent advances in high-dimensional and single-cell assays have elucidated upwards of 20 cell subsets in the RA synovium. This includes novel fibroblast populations and lymphocyte phenotypes, which in many cases exhibit features that have not been found in other tissues thus far.

Summary

Molecular profiling studies over the past several years have rapidly generated a comprehensive and detailed outline of the cellular phenotypes in synovial tissue affected by RA. Molecular features of these newly identified cell subsets immediately represent reasonable therapeutic targets and provide the opportunity to design the most clinically relevant mechanistic experiments. Broadly speaking, the ~ 20 cell types thus far identified in RA synovium seem to be fairly well conserved across patients, despite extensive heterogeneity in patient clinical features, stage of disease, and treatment responses. Thus, a next phase in molecular profiling may benefit from quantifying patient samples in terms of the ratios of cell types, with the rationale that certain cellular interactions will predominate in an individual and medications targeting these interactions may be more efficacious for that individual. Such cellular profiling in tissues combined with studies examining how the compendium of these cells interact in their three-dimensional tissue ultrastructures will be important in understanding how collectively these cells drive the disease process and ultimately how best to treat patients.

Childhood- Versus Adult-Onset Primary Vasculitides: Are They Part of the Same Clinical Spectrum?

Abstract

Purpose of the Review

Most of the primary vasculitis in children and adults has different clinical manifestations for the same disease, which suggests that they might not be part of the same clinical spectrum and requires a different approach in order to reduce the morbidity and mortality of these patients. In this work, we review the most recent literature and the most important studies that describe and compare adult and children primary vasculitides pathogenesis, clinical presentation, and treatment approach. Accordingly, we discuss recent research involving clinical trials, comparison studies, and pathogeny for these vasculitides.

Recent Findings

Clinical manifestations in the different primary vasculitis change in predominance from adults to children. There is a female sex predominance for the ANCA vasculitides in children compared with adults, but the same treatment works in most cases for both groups.

Summary

Identifying the diverse clinical spectrum in both adults and children primary vasculitides will reduce the need to extrapolate the diagnostic criteria from one group to another and individualize it, which will allow the clinician to establish a better approach.

Correction to: Towards a Better Classification and Novel Therapies Based on the Genetics of Systemic Sclerosis
The original version of this article unfortunately contained a mistake. The legend of Fig. 1 was incorrect.

Issues in CPPD Nomenclature and Classification

Abstract

Purpose of Review

This paper covers confusion and challenges in the nomenclature of calcium pyrophosphate deposition disease. Clinicians, investigators, and patients are faced with a variety of terms that are used to describe CPPD and its phenotypes, and clarity is greatly needed to help advance research and patient care. Motivation for the upcoming development of CPPD classification criteria is reviewed.

Recent Findings

EULAR proposed recommended terminology for CPPD in 2011. International Classification of Diseases (ICD-9 and ICD-10) billing codes identify definite or probable CPPD with variable accuracy depending on the clinical setting and comparator group. READ diagnostic codes have been employed to identify pseudogout in UK datasets but their accuracy has not been evaluated. CPPD classification criteria will provide a system for identifying a relatively homogenous group of patients to be included in clinical studies, enabling comparison of outcomes across studies.

Summary

CPPD nomenclature remains challenging for clinicians, investigators, and patients. A lay-friendly definition of CPPD, using easily accessible terminology, would be welcome. CPPD classification criteria are a necessary step in moving forward CPPD clinical research and may involve a range of clinical, laboratory, and imaging modalities.

Cardiovascular Safety of Urate Lowering Therapies

Abstract

Purpose of Review

The effect of urate lowering treatment (ULT) on cardiovascular (CV) risk and mortality in gout has been a topic of interest. This review discusses the CV effect of ULT and comparative CV safety among ULT agents.

Recent Findings

The mechanism linking gout with CV risk is not fully understood but seems multifactorial involving hyperuricemia, xanthine oxidase (XO), oxidative stress, and chronic inflammation. Conflicting data exist regarding CV benefits of ULT in adults with and without hyperuricemia. Although meta-analyses on randomized controlled trials (RCTs) suggest CV benefits with allopurinol, few high-quality RCTs have examined the CV effect of ULT among patients with hyperuricemia or gout. The recent CARES trial adds new information on comparative CV safety between two XO inhibitors (XOIs), febuxostat and allopurinol, in patients with gout.

Summary

It remains unclear whether ULT reduces CV risk in patients with gout or hyperuricemia. Comparative CV safety studies of XOIs suggest that additional mechanisms beyond urate-lowering effect or XO inhibition are likely involved in CV risk modification in patients with gout. Ongoing RCTs of ULT may be able to further determine the effect of ULT on CV risk.

Yoga for Osteoarthritis: a Systematic Review and Meta-analysis

Abstract

Purpose of Review

This study aims to systematically review and summarise the efficacy and safety of yoga for osteoarthritis. Medline (through PubMed), Scopus, and the Cochrane Library were searched through April 2018 for randomised controlled trials of yoga for osteoarthritis. Primary outcomes were pain intensity, function, and quality of life; secondary outcomes were mental health and safety. Risk of bias was assessed using the Cochrane tool and quality of evidence through GRADE.

Recent Findings

Nine trials including 640 individuals with mainly lower extremity osteoarthritis aged 50–80 years were identified, with 80.3% female participants (median). Meta-analyses revealed very low–quality evidence for the effects of yoga on pain (vs. exercise: standardised mean difference (SMD) = − 1.07; 95%CI − 1.92, − 0.21; p = 0.01; vs. non-exercise: SMD = − 0.75; 95%CI − 1.18, − 0.31; p < 0.001), physical function (vs. exercise: SMD = 0.80; 95%CI 0.36; 1.24; p < 0.001; vs. non-exercise: SMD = 0.60; 95%CI 0.30, 0.98; p < 0.001), and stiffness (vs. exercise: SMD = − 0.92; 95%CI − 1.69, − 0.14; p = 0.008; vs. non-exercise: SMD = − 0.76; 95%CI − 1.26, − 0.26; p = 0.003) in individuals with knee osteoarthritis. Effects were not robust against potential methodological bias. No effects were found for quality of life, and depression, or for hand osteoarthritis. Safety was rarely reported.

Summary

The findings of this meta-analysis indicate that yoga may be effective for improving pain, function, and stiffness in individuals with osteoarthritis of the knee, compared to exercise and non-exercise control groups. Due to the low methodological quality and potential risk of bias, only a weak recommendation can be made at this time for the use of yoga in adults with osteoarthritis of the knee.

Innate Immune Dysregulation in the Development of Cardiovascular Disease in Lupus

Abstract

Purpose of Review

The systemic inflammatory nature of systemic lupus erythematosus (SLE) is patent not only in the diverse clinical manifestations of the disease but also in the increased risk of premature cardiovascular diseases (CVD). In this review, we discuss the latest findings on the key factors of the innate immune system known to play critical roles in the pathogenesis of accelerated CVD in patients with SLE and discuss the potential that immunometabolism may play a key role in this respect.

Recent Findings

Recent studies exploring the association between SLE and premature CVD clearly showed that alterations of specific immune functions play a pivotal role in the increased cardiovascular morbidity and mortality in the SLE patients. Novel molecular factors such as type I interferons (IFN), dysregulated neutrophil function, and changes to cellular metabolism and metabolites are emerging as important regulators of systemic immune dysfunction and as strong risk factors for premature CVD in SLE.

Summary

Although corticosteroids and cytotoxic agents can be used to effectively manage and control various lupus-related complications, to date, no drug has been proven to prevent the development of premature atherosclerosis in SLE. However, as new mechanisms underlying this complication of SLE are uncovered, such as the role of metabolism and neutrophil-driven inflammation, new avenues for therapeutic intervention are being discovered.

Takayasu Arteritis: Recent Developments

Abstract

Purpose of Review

Takayasu arteritis (TA) is a granulomatous inflammatory disorder that affects large vessels, especially aorta and its proximal branches. Its diagnosis can be extremely challenging due to the non-specificity of the systemic inflammatory manifestations during the early phase of the disease and usually follows an insidious clinical course until the emergence of vascular ischemic complications.

Recent Findings

Its pathogenesis has been better delineated in recent years, especially the role of HLA-B*52 allele in certain ethnic groups, as well as the use of biological therapy, and surgical revascularization. Recent findings are discussed in depth.

Summary

Clinical and epidemiological aspects of TA, recent developments in pathogenesis, and therapy are presented.

Towards a Better Classification and Novel Therapies Based on the Genetics of Systemic Sclerosis

Abstract

Purpose of the Review

Nowadays, important advances have occurred in our understanding of the pathogenesis of systemic sclerosis (SSc), which is a rare immune-mediated inflammatory disease (IMID) characterized by vascular damage, immune imbalance, and fibrosis. Its etiology remains unknown; nevertheless, both environmental and genetic factors play a major role in the disease. This review will focus on the main advances made in the field of genetics of SSc.

Recent Findings

The assessment of how interindividual genetic variability affects disease onset and progression has enhanced our knowledge of disease biology, and this will eventually translate in the development of new diagnostic and therapeutic tools, which is the final goal of personalized medicine.

Summary

We will provide an overview of the most relevant achievements in the genetics of SSc, its shared genetics among IMIDs with special attention on drug repurposing, current challenges for the functional characterization of risk variants, and future directions.

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